DESCRIPTION (Applicant's Abstract): The health-protective properties of polyphenolic compounds have been increasingly appreciated by the scientific community, based on the accumulation of evidence for cancer-preventative, anti-inflammatory, cardioprotective, and other roles of these phytochemicals from teas, red wines and fruits. Proanthocyanidins have only recently demonstrated important roles in chemoprevention. However, the structural intricacy of individual molecules, the labile nature of compounds, and the complexity of mixtures in which they occur have severely limited study of this group of substances. Because these bioactive compounds are present in many functional foods and nutraceutical isolates, gauging the potency of specific proanthocyanidin entities is of high priority. Mixtures of natural products often have different properties than individual isolated compounds. The physiological and pharmacological roles of mixtures of proanthocyanidins and other phytochemicals in foods and dietary supplements remain challenging and elusive research problems. Novel approaches to the extraction, fractionation, chromatographic separation, isolation and characterization of proanthocyanidin monomers and oligomers now permit evaluation of bioactivity of chemically identified entities, and recombination with other plant natural components to study the role of interactions on biological activity. The three laboratories involved in this project have unique skills in phytochemistry, in vitro technology, and bioactivity assessment that permit resolution of key questions concerning the presence of proanthocyanidins, their interactions with each other and other phytochomicals, and their roles in complex mixtures, as they occur in nature. Knowledge gained in this investigation will define standards for using natural mixtures in therapeutic regimes, identify optimal methods for storage and handling the materials, and pave the way for breeding advances by clarifying the identity of the mixture components needed for maximum benefit of the consumer.